Accurate assessment of renal function is critical for appropriate drug dosing of renally excreted compounds. Glomerular filtration rate (GFR) is considered the best marker of kidney function. Inulin clearance forms the gold standard for measuring GFR, both in adults and in children. The method is invasive, cumbersome, and smaller children require urinary catheterization for accurate timed urine collections. Nuclear medicine methods replaced inulin clearance in the 1970s after (51)Cr EDTA clearance was introduced. Inulin has no plasma protein binding, whereas all commonly used radioisotopes have a small amount of plasma protein binding that leads to lower values. Only iohexol does not have significant plasma protein binding. The underestimation due to plasma protein binding is partially offset by overestimation due to the use of non-compartmental pharmacokinetic modeling of the plasma disappearance of the radioisotope. The problem could be overcome with a urinary nuclear medicine clearance method, but these have not been validated in children. Endogenous markers of GFR include serum creatinine and low molecular weight proteins such as cystatin C and beta-trace protein. Of these, estimation of GFR using cystatin C appears to be the most promising, although its accuracy in pregnancy and in the neonatal period may be limited.
SummaryBackground and objectives The diagnostic accuracy of cystatin C estimated GFR (eGFR) by various cystatin C equations have varied in different studies. We hypothesized that the GFR level of enrolled patients affects the diagnostic accuracy of a cystatin C equation.Design, setting, participants, & measurements We analyzed 240 consecutively enrolled children at a single Canadian center in a prospective and cross-sectional study. Cystatin C was analyzed with nephelometry, and cystatin C eGFR was estimated by the equations validated in children. GFR was measured by technetium-99m-diethylene-triamine penta-acetic acid ( 99m Tc DTPA).Results We compared various cystatin C equations across GFR strata Ͻ60, Ͻ90, Ն135, and Ն150 ml/min per 1.73 m 2 for an accurate prediction and appropriate classification of the measured GFR. The CKiD, Zappitelli-CysEq, and Zappitelli-CysCrEq equations had a higher accuracy, estimated by eGFR values within 10% and 30% of the respective 99m Tc DTPA, in the GFR categories Ͻ60 and Ͻ90 ml/min per 1.73 m 2 , whereas the Bö kenkamp, Bouvet, and Filler equations had a greater accuracy in the GFR categories Ն135 and Ն150 ml/min per 1.73 m 2 . The Bouvet, CKiD, Filler, Zappitelli-CysEq, and Zappitelli-CysCrEq equations had a greater sensitivity to classify GFR Ͻ60 and Ͻ90 ml/min per 1.73 m 2 , whereas the Bö kenkamp equation had a higher sensitivity for GFR Ն135 and Ն150 ml/min per 1.73 m 2 . ConclusionsThe diagnostic accuracy of various cystatin C equations varies with GFR. This issue needs consideration while applying these equations in clinical practice and for further research on eGFR equations.
According to the Barker hypothesis, intrauterine growth restriction and premature delivery adversely affect cardiovascular health in adult life. The association of childhood hypertension as a cardiovascular risk factor and birth weight has been understudied. In a prospective cohort study, the authors evaluated the effect of birth weight, gestational age, maternal prepregnancy body mass index (BMI), and child BMI z score at the time of enrollment on the systolic and diastolic blood pressure (BP) z score in 3024 (1373 women) consecutive outpatient clinic patients aged 2.05 to 18.58 years. The latest National Health and Nutrition Examination Survey (NHANES III) was used to calculate the age‐dependent z scores. The median z scores of BMI (+0.48, range −6.96–6.64), systolic BP (+0.41, range −4.50–6.73), and diastolic BP (+0.34, range −3.15–+6.73) were all significantly greater than the NHANES III reference population. Systolic BP z score did not correlate with birth weight or gestational age, but did correlate with maternal prepregnancy BMI (r=.090, P<.0001) and BMI z score (r=.209, P<.0001). Diastolic BP z score positively correlated with birth weight (0.037, P=.044), gestational age (r=.052, P=.005), BMI z score(r=.106, P<.0001), and maternal prepregnancy BMI (r=.062, P=.0007). In contrast to what would be expected from the Barker hypothesis, the authors found no negative correlation between BP z score and birth weight or gestational age. This study suggests that a high BMI, a big mom, and a high birth weight are more important risk factors for hypertension during childhood than low birth weight or gestational age. J Clin Hypertens (Greenwich). 2011;13:35–41. ©2010 Wiley Periodicals, Inc.
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